The big problem remaining in modern medicine is said to overcome deficiency of organs due to disease or external injuries, and functional impairment. The only method that can be practiced today for treating such condition is organ transplantation. However, there are still many difficulties for spreading as an actual therapeutic method, due to problems such as brain-death diagnosis or supply from donors. On the other hand, regenerative medicine intending regeneration of organs draws attention with the recent development of stem cells and developmental biology, and is expected as the direction of the medicine to advance in the 21st century. In animal experiment level, functional recoveries of organs by transplantation of embryonic stem cells (ES cells) have been reported, while at present, the application in human is coming up against a brickwall due to rejection or ethical problems of the use of ES cells. Further, as various adult tissue stem cells (mesenchymal, blood vessels, liver etc.) are extremely few in vivo, the isolation thereof is technically difficult, and it is hard at the present time to obtain sufficient amount of cells for transplantation. Therefore, there are many problems to be solved before the regenerative medicine using ES cells or tissue stem cells can be applied to the actual medicine. Particularly, it is essential to have a stable supply of cells having differentiation potential so that regenerative medicine by cell transplantation becomes a reality.
The present inventors have found first in the world, that human peripheral blood monocyte-derived cells have a potential to differentiate into bone, cartilage, skeletal muscle, fat, cardiac muscle, vascular endothelial and neurons under a particular culture condition (nonpatent documents 1 to 4, patent document 1), and have named this novel cell as monocyte-derived multipotent cell (MOMC). As monocytes can be easily collected from peripheral blood largely non-invasively, it can be obtained in a relatively simple manner. Further, as it represents about 20% of peripheral blood mononuclear cells, cells can be provided stably in a necessary and sufficient amount. Further, as MOMC can be produced from monocytes from a subject to be administered, there are no problems for securing donors or of rejection, and there are almost no ethical problems. Specifically, it can be said that MOMC is a multipotent cell that is very suitable for cell transplantation, for actual organ regeneration. Patent Document 1 filed by the present inventors describes a method for producing MOMC by inducing differentiation of peripheral blood monocytes into MOMC by using CD14− cells. By utilizing the present method, differentiation induction from monocytes into MOMC can be conducted simply, rapidly and at a low cost, without using a particular device. Further, the present inventors have previously found that it is necessary to coculture with platelets and not with lymphocytes for inducing MOMC from peripheral blood monocytes (Nonpatent Document 5).
On the other hand, Patent Document 2 discloses a method for forming P stem cells comprising transforming mononuclear cells to P stem cells with protein kinase C bII of activated mononuclear cell, and also describes to use GM-CSF, SDF or a combination thereof as protein kinase C conditioner. Patent document 2 further describes that P stem cell can be differentiated into cartilage cells, neurons or osteocytes. Moreover, P stem cell is a cell that can be obtained by a culture on either collagen or fibronectin (see “specific example 3 of Example 1” of Patent Document 2).
Moreover, SDF-1 (Stromal Derived Factor 1) is one kind of cytokine that performs growth, differentiation and functional expression of cells (nonpatent document 6). Cytokines include a large variety of proteins, and the followings are well known: interleukin (IL), colony stimulating factor (CSF), stem cell factor (SCF), tumor necrosis factor (TNF), interferon (IFN), transforming growth factor (TGF), bone morphogenic protein (BMP), epidermal growth factor (EGF), keratinocyte growth factor (KFG), fibroblast growth factor (FGF), insulin-like growth factor (IGF), platelet-derived growth factor (PDGF), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEFG), macrophage inflammatory protein (MIP), monocyte chemotactic protein (MCP), and RANTES. Among these, those that have been found as a series of cytokines dominating the migration activity and activation of a specific leukocyte subset are particularly called chemokines. Chemokines contain conserved cysteine residues (Cys) in the molecule, and are classified into four subfamilies (CXC, CC, C, CX3C) based on their position in the molecule structure. SDF-1 is a CXC-type chemokine, and SDF-1 receptor is known to be CXCR4, which is one of the CXC chemokine receptors.
As it is stated in the above, the method for producing MOMC was known from patent document 1, while a more useful method for producing MOMC with a higher MOMC differentiation efficiency was awaited. However, it has not been known at all whether SDF-1 affects the differentiation-inducing efficiency from peripheral blood monocytes into MOMC.    Patent Document 1: Japanese Patent No. 3762975    Patent Document 2: Japanese Published Patent Application No. 2006-333866    Nonpatent Document 1: J Leukoc Biol, 2003, 74, 833-45    Nonpatent Document 2: Stem Cell Dev, 2005, 14, 676-86    Nonpatent Document 3: Immunol Cell Biol, 2006, 84, 209-17    Nonpatent Document 4: Stem Cells, 2006, 84, 2733-43    Nonpatent Document 5: The Japanese Society of Inflammation and Regeneration, Abstracts W-7-4, “Investigation on the induction process of human monocytes derived-multipotent cells”, Published on July 2007    Nonpatent Document 6: Science, 1993, 261, 600-603